| Description: |
Psoralidin possesses potent antidepressant-like, anti-inflammatory, anticancer and chemopreventive properties. Psoralidin is a dual inhibitor of COX-2 and 5-LOX, it is also an agonist for both estrogen receptor (ER)α and ERβ agonist.Psoralidin inhibits LPS-induced iNOS expression via repressing Syk-mediated activation of PI3K-IKK-IκB signaling pathways, it induces reactive oxygen species (ROS)-dependent DNA damage and protective autophagy mediated by NOX4 in breast cancer cells.
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| Targets: |
PI3K | Akt | NF-kB | Caspase | Estrogen receptor | COX | LOX | PGE | TNF-α | TGF-β/Smad | IL Receptor | Chk | ROS | NO | PI3K | NOS | IkB | 5-HT Receptor | IKK | Progestogen receptor |
| In vitro: |
| Phytomedicine. 2016 Aug 15;23(9):939-47. | | Psoralidin induced reactive oxygen species (ROS)-dependent DNA damage and protective autophagy mediated by NOX4 in breast cancer cells.[Pubmed: 27387402] | Psoralidin (PSO), a natural phenolic coumarin, was reported to have anti-cancer activities. PSO induced reactive oxygen species (ROS) generation in cancer cells. The role of ROS in its anti-cancer effect remains unclear.
This study was designed to investigate the potential roles of ROS in PSO-induced anti-cancer effect in MCF-7 breast cancer cells.
METHODS AND RESULTS:
Effect of PSO on cancer cell proliferation was determined by MTT assay. Comet assay was used to determine DNA damage. Protein expression was detected by Western blotting. Autophagic vacuoles were detected by monodansylcadaverine (MDC) staining. ROS generation was measured by fluorescent probe. NOX4 localization was determined by immunofluorescence staining.
PSO treatment caused proliferation inhibition in time- and dose- dependent manners, which was partially reversed by N-acetyl cysteine (NAC) and diphenyleneiodonium (DPI). PSO induced DNA damage and increased protein expression of γ-H2AX, phosphorylation of ATM, ATR, Chk1, and Chk2. PSO induced autophagy as evidenced by the accumulation of autophagic vacuoles and alterations of autophagic protein expression. PSO-induced cell death was enhanced by autophagy inhibitor chloroquine (CQ). Furthermore, PSO treatment induced ROS formation, which was reversed by NAC or DPI pretreatment. The expression of NOX4 was significantly enhanced by PSO. Both NAC and DPI could reverse PSO-induced DNA damage and autophagic responses. In addition, silencing NOX4 by siRNA inhibited PSO-induced ROS generation, DNA damage, and autophagy.
CONCLUSIONS:
Taken together, these results showed that PSO induced DNA damage and protective autophagy mediated by ROS generation in a NOX4-dependent manner in MCF-7 cells. | | Molecules. 2012 May 29;17(6):6449-64. | | The coumarin psoralidin enhances anticancer effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).[Pubmed: 22643355 ] | Coumarins are a very common type of secondary plant metabolites with a broad spectrum of biological activities. Psoralidin is a naturally occurring furanocoumarin isolated from Psoralea corylifolia possessing anticancer and chemopreventive properties. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cancer cells with no toxicity toward normal tissues. Endogenous TRAIL plays an important role in immune surveillance and defence against cancer cells. Coumarins can modulate TRAIL-mediated apoptosis in cancer cells.
METHODS AND RESULTS:
We examined the cytotoxic and apoptotic activities of Psoralidin in combination with TRAIL on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining and mitochondrial membrane potential was evaluated using DePsipher staining by fluorescence microscopy. Death receptor (TRAIL-R1/DR4 and TRAIL-R2/DR5) expression was analyzed using flow cytometry. Psoralidin enhanced TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2 death receptor and depolarization of mitochondrial membrane potential.
CONCLUSIONS:
Our study indicated that Psoralidin augmented the anticancer effects of TRAIL and confirmed a potential use of coumarins in cancer chemoprevention. | | Planta Med. 1996 Aug;62(4):353-4. | | The cytotoxicity of psoralidin from Psoralea corylifolia.[Pubmed: 8792669] | | A cytotoxic coumestan derivative, psoralidin (1), was isolated from the seed of Psoralea corylifolia. The IC50 values of 1 against SNU-1 and SNU-16 carcinoma cell lines were 53 and 203 micrograms/ml, respectively, indicating cytotoxic activity against stomach carcinoma cell lines. |
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| In vivo: |
| Biochem Pharmacol. 2011 Sep 1;82(5):524-34. | | Psoralidin, a dual inhibitor of COX-2 and 5-LOX, regulates ionizing radiation (IR)-induced pulmonary inflammation.[Pubmed: 21669192] | Psoralidin, a coumestan derivative isolated from the seed of Psoralea corylifolia, has been studied for anti-cancer and anti-bacterial properties. However, little is known regarding its effects on IR-induced pulmonary inflammation. The aim of this study is to investigate mechanisms of IR-induced inflammation and to examine therapeutic mechanisms of Psoralidin in human normal lung fibroblasts and mice.
METHODS AND RESULTS:
Here, we demonstrated that IR-induced ROS activated cyclooxygenases-2 (COX-2) and 5-lipoxygenase (5-LOX) pathway in HFL-1 and MRC-5 cells. Psoralidin inhibited the IR-induced COX-2 expression and PGE(2) production through regulation of PI3K/Akt and NF-κB pathway. Also, Psoralidin blocked IR-induced LTB(4) production, and it was due to direct interaction of Psoralidin and 5-lipoxygenase activating protein (FLAP) in 5-LOX pathway. IR-induced fibroblast migration was notably attenuated in the presence of Psoralidin. Moreover, in vivo results from mouse lung indicate that Psoralidin suppresses IR-induced expression of pro-inflammatory cytokines (TNF-α, TGF-β, IL-6 and IL-1 α/β) and ICAM-1.
CONCLUSIONS:
Taken together, our findings reveal a regulatory mechanism of IR-induced pulmonary inflammation in human normal lung fibroblast and mice, and suggest that Psoralidin may be useful as a potential lead compound for development of a better radiopreventive agent against radiation-induced normal tissue injury. |
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